Lifestyle and Risk of Screening‐Detected Abdominal Aortic Aneurysm in Men

Stackelberg, Otto; Wolk, Alicja; Eliasson, Ken; Hellberg, Anders; Bersztel, Adam; Larsson, Susanna C.; Orsini, Nicola; Wanhainen, Anders; Björck, Martin

doi:10.1161/jaha.116.004725

Cited by 48 publications

(62 citation statements)

References 37 publications

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“…Abrogation of this cytokine, in animal models, has demonstrated efficacy in decreasing aneurysm diameter growth. 2 Although several putative autoantigens have been proposed, the true causative antigen has yet to be identified. 3 We think aneurysm initiation can be divided into 2 stages: sensitization followed by chronic inflammation.…”

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confidence: 99%

Immune Modulation as a Treatment for Abdominal Aortic Aneurysms

Wang

Murphy

2018

Circulation Research

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In the United States, >200 000 new patients are diagnosed with abdominal aortic aneurysm (AAA) each year. Consequently, >40 000 highly morbid aortic reconstructions are performed each year to prevent aneurysm rupture, a catastrophic event associated with near-certain mortality. No pharmaceutical currently exists to slow aneurysm growth, but a 50% reduction in diameter growth per annum could halve the number of aortic reconstructions required. Therefore, successful use of cell therapy to modulate chronic inflammation hallmark to AAA to slow diameter expansion represents a potentially paradigmaltering treatment.There continues to be no US Food and Drug-approved medication to slow or stop AAA growth. This deficit is certainly not because of a lack of effort over the previous decades. Initial investigations focused on the reduction of mechanical stress through decreasing blood pressure and sac pressurization cycles; however, clinical trials investigating drugs, such as, angiotensin II-converting enzyme inhibitors, angiotensin receptor blockers, and β-blockers, all failed to demonstrate a therapeutic reduction of diameter growth compared with placebo. Next, the inhibition of matrix metalloproteinases was trialed with doxycycline, an antibiotic inhibitor of matrix metalloproteinases 2 and 9. Doxycycline also treats species of Chlamydia, which were isolated from the aortic walls of a minority of aneurysmal arteries. Although initial uncontrolled results were promising, therapeutic response was not replicated in large randomized studies. Last, aortic wall inflammation was targeted using statins, a ubiquitous anti-inflammatory, lipid-lowering drug to limited success. The discovery of a nonsurgical treatment for AAA is contingent on the robust understanding of disease pathogenesis, which continues to be nebulous at best.AAA risk factors, such as, tobacco abuse, advancing age, uncontrolled hypertension, male sex, and white ethnicity, have all been well described but fail to provide evidence elucidating pathogenesis. Regardless, existing evidence implicates that disease initiation is multifactorial with a strong genetic element.There has been a focus of late toward the role of autoimmune mechanisms in AAA formation. The characterization of aortic wall inflammation consisting of mononuclear infiltrates, immunoglobulins, cytokines, and proteases implicate both a host innate and adaptive response. Of note, concentrations of CD4 + T cells have been recently discovered in the periadventitial vascular-associated lymphatic tissue expressing identical T cell receptors, against a currently unknown antigen, and therefore clonally expanded, providing crucial evidence for AAA as an autoimmune disease.1 Moreover, interleukin (IL)-17, a cytokine elaborated from the antigen-specific Th17 lymphocyte and overexpressed in autoimmune disorders, is highly expressed in the AAA condition. Abrogation of this cytokine, in animal models, has demonstrated efficacy in decreasing aneurysm diameter growth.2 Although several putative autoantigens have b...

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confidence: 99%

Immune Modulation as a Treatment for Abdominal Aortic Aneurysms

Wang

Murphy

2018

Circulation Research

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“…; Stackelberg et al. ). A meta‐analysis of AAA demonstrated that AAA prevalence was high in patients with coronary artery disease (8.4%) (Elkalioubie et al.…”

Section: Introductionmentioning

confidence: 98%

“…; Stackelberg et al. ), the AAA prevalence was still over 1% in men between 65 and 75 years of age (Jacomelli et al. ; Stackelberg et al.…”

Section: Introductionmentioning

confidence: 99%

“…Abdominal aortic aneurysm (AAA) is a relatively common progressive lethal disease among the elderly in most countries (Mani et al 2011), but there is currently no proven medical therapy. Although recent studies in developed countries indicate that AAA prevalence has declined as a result of changes in lifestyle and pharmacological treatment of cardiovascular risk factors, such as lipid-lowering drugs (Jacomelli et al 2016;Stackelberg et al 2017), the AAA prevalence was still over 1% in men between 65 and 75 years of age (Jacomelli et al 2016;Stackelberg et al 2017). A meta-analysis of AAA demonstrated that AAA prevalence was high in patients with coronary artery disease (8.4%) (Elkalioubie et al 2015).…”

Section: Introductionmentioning

confidence: 99%

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A selective antagonist of prostaglandin E receptor subtype 4 attenuates abdominal aortic aneurysm

Yokoyama

Saito

et al. 2018

Physiol Rep

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Abdominal aortic aneurysm (AAA) is a progressive disease that has an increasing prevalence with aging, but no effective pharmacological therapy to attenuate AAA progression is currently available. We reported that the prostaglandin E receptor EP4 plays roles in AAA progression. Here, we show the effect of CJ‐42794, a selective EP4 antagonist, on AAA using two mouse models (angiotensin II‐ and CaCl2‐induced AAAs) and human aortic smooth muscle cells isolated from AAA tissue. Oral administration of CJ‐42794 (0.2 mg/kg per day) for 4 weeks significantly decreased AAA formation in ApoE−/− mice infused with angiotensin II (1 μg/kg per min), in which elastic fiber degradation and activations of matrix metalloproteinase (MMP)‐2 and MMP‐9 were attenuated. Interleukin‐6 (IL‐6) proteins were highly expressed in the medial layer of angiotensin II‐induced mouse AAA tissues, whereas this expression was significantly decreased in mice treated with CJ‐42794. AAA formation induced by periaortic CaCl2 application in wild‐type mice was also reduced by oral administration of CJ‐42794 for 4 weeks. After oral administration of CJ‐42794 beginning 2 weeks after periaortic CaCl2 application and continuing for an additional 4 weeks, the aortic diameter and elastic fiber degradation grade were significantly smaller in CJ‐42794‐treated mice than in untreated mice. Additionally, in smooth muscle cells isolated from human AAA tissues, stimulation of CJ‐42794 inhibited PGE 2‐induced IL‐6 secretion in a dose‐dependent manner and decreased PGE 2‐induced MMP‐2 activity. These data suggest that inhibition of EP4 has the potential to be a pharmacological strategy for attenuation of AAA progression.

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“…Izuzetno, može se videti i pri nativnoj radiografiji abdomena ukoliko su zidovi aneurizme izuzetno kalcifikovani [6]. U svetu su sprovedene četiri velike randomizovane, kontrolisane studije na opštoj populaciji, koje su se bavile skriningom AAA u periodu od 1991. do 2004. godine (Čičester studija, Velika Britanija; Zapadnoaustralijska studija u Pertu, Australija; Viborg studija, Danska; MASSmulticentrična skrining studija -Oksford, Portsmut, Vinčester i Sauthempton: Velika Britanija), sa ukupnim brojem obuhvaćene populacije od skoro 140.000 ljudi [7][8][9]. U svim studijama je ultrazvuk (UZ) istaknut kao metoda izbora za rani skrining AAA zbog jednostavnosti izvođenja, niskih troškova, neinvazivnosti, kao i bez upotrebe jonizujućeg zračenja za razliku od MSCTa, sa visokom senzitivnošću i specifičnošću od 97% [6].…”

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The importance of ultrasound diagnostics in aortic aneurysm detection in the municipal institution for emergency medical aid infirmary, Belgrade

Stefanović¹,

Stevović-Gojgić²,

Čolaković³

et al. 2019

NČ urgent medic Halo 194

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Uvod Aneurizma abdominalne aorte (AAA) je oboljenje sredovečnih muškaraca koje je često asimptomatsko, sa visokim rizikom od razvoja komplikacija. Najopasnija komplikacija je njena ruptura koja ima izuzetno visok procenat smrtnosti. U svetu je ultrazvučna dijagnostika široko priznata kao metoda ranog skrininga za AAA. Cilj rada Prikazati važnost ultrazvučnog pregleda abdomena u ranoj detekciji i opisu karakteritika AAA kod pacijenata pregledanih u ambulanti za ultrazvuk u GZZHMP Beograd. Metod rada Podaci su dobijeni iz protokola ambulante za ultrazvuk i elektronskih zapisa izveštaja datih pacijentima u GZZHMP Beograd, a potom obrađeni deskriptivnim statističkim metodama. Pregled je vršio subspecijalista za ultrazvuk u kliničkoj medicini na aparatu GE, sondom od 3,5 MHz. Rezultati U toku 2015. godine obavljeno je 1.407 pregleda. Dijagnoza Aneurysma aorte abdominalis postavljena je kod 48 pacijenata (3,4%), od toga 37 muškaraca (77,1%) i 11 žena (22,9%). Najučestalije oboleli su osobe starosti 60-79 godina (83%). Kao važni faktori rizika izdvojili su se pušenje 66,7%, povišene vrednosti masti u krvi 81,3%, hiperglikemija 60,4%, hipertenzija 87,5%, fizička neaktivnost 70,8%. Više od 50% pacijenata je imalo simptome u vidu bola u donjem delu leđa i osećaja jakih pulzacija u trbuhu. Preko 80% je imalo dijametar AAA 30-45mm. Pozicija AAA je najčešće u infrarenalnom segmentu aorte (85,4%). Veoma često je jedno aneurizmatsko proširenje (64,6%) sa parijetalnim trombom na jednom zidu (56,3%). Zaključak Ultrazvuk abdomena je pouzdana, jednostavna i precizna metoda u ranom otkrivanju AAA u ambulanoj službi GZZHMP.

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Lifestyle and Risk of Screening‐Detected Abdominal Aortic Aneurysm in Men

Cited by 48 publications

References 37 publications

Immune Modulation as a Treatment for Abdominal Aortic Aneurysms

Immune Modulation as a Treatment for Abdominal Aortic Aneurysms

A selective antagonist of prostaglandin E receptor subtype 4 attenuates abdominal aortic aneurysm

The importance of ultrasound diagnostics in aortic aneurysm detection in the municipal institution for emergency medical aid infirmary, Belgrade

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